Peter Dodek, MD, MHSc; Sean Keenan, MD, MSc(Epid); Deborah Cook, MD, MSc(Epid); Daren Heyland, MD, MSc(Epid); Michael Jacka, MD, MSc; Lori Hand, RRT; John Muscedere, MD; Debra Foster, RN; Nav Mehta, MD; Richard Hall, MD; Christian Brun-Buisson, MD; for the Canadian Critical Care Trials Group and the Canadian Critical Care Society
Acknowledgments: The authors thank the Canadian Critical Care Trials Group and Canadian Critical Care Society for their support of this initiative and the professional societies who reviewed and critiqued this guideline. The VAP Prevention Guideline Panel thanks Dr. John Heffner for his advice during the development of this guideline.
Grant Support: By an unrestricted grant from Pfizer Canada Inc. Dr. Cook is a chair of the Canadian Institutes for Health Research. Dr. Heyland is a Career Scientist of the Ontario Ministry of Health and Long-Term Care.
Potential Financial Conflicts of Interest:Grants received: D. Cook (Hoechst Marion Roussel, Glaxo Wellcome), D. Heyland (Bayer Inc., AstraZeneca), C. Brun-Buisson (Wyeth-Lederle).
Requests for Single Reprints: Peter Dodek, MD, MHSc, Center for Health Evaluation and Outcome Sciences, St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada; e-mail, email@example.com.
Current Author Addresses: Dr. Dodek: St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada.
Dr. Keenan: Suite 103, 250 Keary Street, New Westminster, British Columbia V3L 5E7, Canada.
Dr. Cook and Ms. Hand: McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Dr. Heyland: Kingston General Hospital, 76 Stuart Street, Kingston, Ontario K7L 2V7, Canada.
Dr. Jacka: University of Alberta, 1051 Falconer Road, Edmonton, Alberta T6R 2C9, Canada.
Dr. Muscedere: Hotel-Dieu Grace Hospital, 1030 Ouellette Avenue, Windsor, Ontario N91 1E1, Canada.
Ms. Foster: Department of Critical Care, University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
Dr. Mehta: Sudbury Regional Hospital, 41 Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada.
Dr. Hall: Queen Elizabeth II Health Sciences Center, 1796 Summer Street, Room 5452 HI, Halifax, Nova Scotia B3H 3A7, Canada.
Dr. Brun-Buisson: Department of Medical Intensive Care and Infection Control Unit, Hopital Henri Mondor, 51, avenue du Mal de Lattre de Tassigny, 94010 Creteil Cedex, France.
Ventilator-associated pneumonia (VAP) is an important patient safety issue in critically ill patients.
To develop an evidence-based guideline for the prevention of VAP.
MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews.
The authors systematically searched for relevant randomized, controlled trials and systematic reviews that involved mechanically ventilated adults and were published before 1 April 2003.
Physical, positional, and pharmacologic interventions that may influence the development of VAP were considered. Independently and in duplicate, the authors scored the validity of trials; the effect size and confidence intervals; the homogeneity of results; and safety, feasibility, and economic issues.
Recommended: The orotracheal route of intubation, changes of ventilator circuits only for each new patient and if the circuits are soiled, use of closed endotracheal suction systems that are changed for each new patient and as clinically indicated, heat and moisture exchangers in the absence of contraindications, weekly changes of heat and moisture exchangers, and semi-recumbent positioning in the absence of contraindications. Consider subglottic secretion drainage and kinetic beds. Not recommended: Sucralfate to prevent VAP in patients at high risk for gastrointestinal bleeding and topical antibiotics to prevent VAP. Because of insufficient or conflicting evidence, no recommendations were made about systematically searching for maxillary sinusitis, chest physiotherapy, the timing of tracheostomy, prone positioning, prophylactic intravenous antibiotics, or intravenous plus topical antibiotics.
No formal economic analysis was performed, and patient perspectives were not considered.
If effectively implemented, this guideline may decrease the morbidity, mortality, and costs of VAP in mechanically ventilated patients.
Table 1. Semi-quantitative Scores of Strategies To Prevent Ventilator-Associated Pneumonia
Table 2. Agreement Scores of Panel Members with the Final Status of Each Item
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James R. Johnson
VA Medical Center, Minneapolis, MN
September 26, 2004
Gut decontamination to prevent VAP
To the editor,
In their guidelines for prevention of ventilator-associated pneumonia, Dodek et al. make no recommendation regarding selective digestive tract decontamination (SDD), despite the solid evidence of its efficacy, because of persisting uncertainty regarding costs and the possible risk of selecting for resistant organisms (1). Their assessment was based on a review of studies published through April 2003. However, in September 2003, de Jonge et al. reported a large trial of SDD that showed significant reductions not only in infections (including ventilator- associated pneumonia) but also in mortality and, most strikingly, the prevalence of antimicrobial-resistant bacteria (2). It would be interesting to know the guidelines panel's opinion regarding whether this added evidence is sufficient to support a recommendation for SDD as a desirable intervention, even if only for selected patients, as others have argued (3), or if further study, especially in a setting with a higher background prevalence of methicillin-resistant staphylococci and/or vancomycin-resistant enterococci, is still needed.
1. Dodek P, Keenan S, Cook D, et al.; Canadian Critical Care Trials Group; Canadian Critical Care Society. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med. 2004 ;141:305-13.
2. de Jonge E, Schultz MJ, Spanjaard L, et al. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet. 2003;362:1011-6.
3. Aarts MA, Marshall JC. In defense of evidence: the continuing saga of selective decontamination of the digestive tract. Am J Respir Crit Care Med. 2002;166:1014-5.
Hendrik K van Saene
University of Liverpool
December 6, 2004
THE EMPEROR'S NEW CLOTHES
TO THE EDITOR: Dodek and colleagues' evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia1 illustrates that the original Canadian promoters of examination of evidence from clinical research do not escape the fate of becoming experts after little more than a decade of evidence-based medicine [EBM]2. Selective decontamination of the digestive tract [SDD] "“ albeit the only ICU intervention with a grade A recommendation from the Agency for Health Research and Quality of the US Department for Health and Human Services3 "“ was not granted a recommendation by a panel of experts selected by the Canadian Critical Care Trials group and the Canadian Critical Care Society due to their low scoring for safety and costs of SDD.
Remarkably, the panel of 11 experts, decided to review only systematic reviews of randomised controlled trials [RCTs] of SDD, whereas they reviewed RCTs for the other interventions. However, of the meta- analyses three4-6 incorporate non-RCTs, three conducted by the Cochrane7-9 were updates of the same meta-analysis of only RCTs, and one was a translation of the first update of Cochrane systematic review from English into Swedish10. Therefore, the panel only assessed four instead of 10 meta -analyses. We would like to clarify our disagreement with the panel's conclusion using the latest Cochrane Library meta-analysis, as its authors applied a well recognised methodology9.
Firstly, a poor score of 1 for the safety of SDD implies that the existent data supports a potential link between antimicrobial resistance and SDD. An analysis of resistance requires the distinction of the number of patients with infections due to resistant aerobic Gram-negative bacilli [AGNB] from patients with infections due to methicillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]. Additionally, low level evidence studies including before-after studies are distinguished from RCTs and long-term resistance studies providing high level of evidence. Again, the meta-analyses evaluated by the panel do not provide data for a link between SDD and antimicrobial resistance. The Cochrane Library meta-analysis "“ the only one that includes the first ever RCT on antimicrobial resistance11 "“ reports that SDD does not lead to resistance amongst AGNB but, even better, the addition of enteral polymyxin/tobramycin to the parenteral antimicrobials reduces resistance compared with the parenteral antibiotics only. This is in line with a previous RCT demonstrating that enteral antimicrobials control extended spectrum beta-lactamase producing Klebsiella12. SDD implemented in two American ICUs with endemic VRE did not lead to an increased number of VRE infections13,14. SDD is not designed to control MRSA. There are seven RCTs conducted in ICUs where MRSA was endemic at the time of the trial, so they report a trend towards higher MRSA infection rates in patients receiving SDD15-21. The addition of enteral vancomycin to SDD is required to control MRSA in ICUs with endemic MRSA22,23. VRE did not emerge in any of the RCTs using enteral vancomycin22-29. Antimicrobial resistance, being a long term issue, has been evaluated in eight SDD studies monitoring antimicrobial resistance between two and seven years, and bacterial resistance associated with SDD has not been a clinical problem30-37.
Secondly, SDD was also given the lower score of 1 for the outcome measure of costs, implying a higher cost to implement SDD on ICU. This is despite the statement "˜Cost-effectiveness of SDD is of unknown magnitude' in the text1. This panel's opinion contrasts the conclusion of the recent report of the Agency for Health Research and Quality of the US Department for Health and Human Services that SDD is cheap and easy to implement3. Fair enough, the cost-effectiveness of SDD is not yet properly assessed, but, costs can hardly be a major concern for a manoeuvre of $6 a day that reduces pneumonia by 65% and mortality by 22% without antimicrobial resistance emerging in unselected ICU patients. This is even more surprising when physiotherapy with its attendant staff costs is considered a low cost strategy.
The conclusion of the Canadian panel that no recommendation could be made about SDD for the prevention of pneumonia during ventilation is not based on evidence from RCTs but on the opinion of the panel, i.e., the lowest level of evidence. Finally, can we remind the panel members and their followers that on average for every five patients who do not receive SDD one extra patient develops a pneumonia and that there is one extra death every 21 patients in units who do not administer SDD. EBM-guidelines should be developed by a critical analysis of the available scientific data with clearly described methodology. The Canadian guidelines do not meet these requirements. Despite the claims of a rigorous evidence base, the members of the panel are not dressed in the robes of EBM but as in the fairy tale "˜The Emperor's New Clothes, they are bare38.
Miguel Angel de la Cal Dept Critical Care Medicine, Getafe Hospital, Madrid, Spain
Luciano Silvestri Dept Anaesthesia and Critical Care, Gorizia Hospital, Italy
Paul Baines Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, UK
Hendrik van Saene Dept Medical Microbiology, University of Liverpool, UK
1. Dodek P, Keenan S, Cook D, Heyland D, Jacka M, Hand L et al. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann Intern Med 2004; 141: 305-313. 2. Sackett DL. The sins of expertness and a proposal for redemption. BMJ 2000; 320: 1283. 3. Collard HR, Saint S. Preventive practices for ventilator-associated pneumonia. In: Shojania KG, Duncan BW, McDonald KM, Wachter RM eds. Making Health Care Safer: A Critical Analysis of Patient Safety Practices. Evidence Report/Technology Assessment No 43. Agency for Healthcare Research and Quality publication 01 "“ E058. Rockville, MD, Agency for Healthcare Research and Quality; 2001. 4. Vandenbroucke-Grauls CM, Vandenbroucke JP. Effect of selective decontamination of the digestive tract on respiratory tract infections and mortality in the intensive care unit. Lancet 1991; 338: 859-862. 5. Hurley JC. Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection? Antimicrob Agents Chemother 1995; 39: 941-947. 6. van Nieuwenhoven CA, Buskens E, van Tiel FH, Bonten MJ. Relationship between methodological trial quality and the effects of selective digestive decontamination on pneumonia and mortality in critically ill patients. JAMA 2001; 286: 335-340. 7. Selective Decontamination of the Digestive Tract Trialists' Collaborative Group. Meta-analysis of randomized controlled trials of selective decontamination of the digestive tract. BMJ 1993; 307: 525-532. 8. D'Amico R, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberti A on behalf of the study investigators. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomized controlled trials. BMJ 1998; 316: 1275-1285. 9. Liberati A, D'Amico R, Pifferi S, Torri V, Brazzi L. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care [Cochrane Review]. In: The Cochrane Library, Issue 1, 2004, Chichester, UK: John Wiley & Sons Ltd. 10. Tonnesen EK, Toft P. Antibiotic prophylaxis in adult critically ill patients in intensive care units. Ugeskr Laeger 1999; 161: 15-17. 11. de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PMM, Vroom MB, Dankert J et al. Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003; 362: 1011-1016. 12. Brun Buisson C, Legrand P, Rauss A, Richard C, Montravers F, Besbes M et al. Intestinal decontamination for control of nosocomial multi- resistant Gram-negative bacilli. Ann Intern Med 1989; 110: 873-881. 13. Arnow PM, Carandang GR, Zabner R, Irwin ME. Randomised controlled trial of selective bowel decontamination for prevention of infections following liver transplantation. Clin Infect Dis 1996; 22: 997-1003. 14. Hellinger WC, Yao JD, Alvarez S, Blair JE, Cowley JJ, Paya CV et al. A randomised, prospective, double-blind evaluation of selective bowel decontamination in liver transplantation. Transplantation 2002; 73: 1904- 1909. 15. Ferrer M, Torres A, Gonzalez J, de la Bellacasa JP, El-Ebiary M, Roca M et al. Utility of selective digestive decontamination in mechanically ventilated patients. Ann Intern Med 1994; 120: 389-395. 16. Gastinne H, Wolff M, Delatour F, Faurisson F, Chevret S for the French Study Group on Selective Decontamination of the Digestive Tract. N Engl J Med 1992; 326: 594-599. 17. Hammond JMJ, Potgieter PD, Saunders GL, Forder AA. Double-blind study of selective decontamination of the digestive tract in intensive care. Lancet 1992; 340: 5-9. 18. Lingnau W, Berger J, Javorsky F, Lejeune Ph, Mutz N, Benzer H. Selective intestinal decontamination in multiple trauma patients: prospective, controlled trial. J Trauma 1997; 42: 687-694. 19. Verwaest Ch, Verhaegen J, Ferdinande P, Schetz M, van den Berge G, Verbist L, Lauwers P. Randomised, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multi disciplinary intensive care unit. Crit Care Med 1997; 25: 63-71. 20. Wiener J, Itokazu G, Nathan C, Kabins SA, Weinstein RA. A randomized, double-blind, placebo-controlled trial of selective digestive decontamination in a medical-surgical intensive care unit. Clin Infect Dis 1995; 20: 861-867. 21. de la Cal MA, Cerda E, Garcia-Hierro P, van Saene HKF, Gomez-Santos D, Negro E, Lorente JA. Survival benefit in critically ill burned patients receiving selective decontamination of the digestive tract: A randomised, placebo-controlled, double-blind trial. Ann Surg 2004: published on line. 22. Sanchez M, Mir N, Canton R et al. The effect of topical vancomycin on acquisition, carriage and infection with methicillin-resistant Staphylococcus aureus in critically ill patients. A double-blind, randomized, placebo-controlled study. 37th ICAAC, 1997 Toronto, Canada, Abstract J-119, page 310. 23. Silvestri L, van Saene HKF, Milanese M et al. Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial. Eur Respir J 2004; 23: 921-926. 24. Bergmans DCJJ, Bonten MJM, Gaillard CA, Paling JC, van der Geest S, van Tiel FH et al. Prevention of ventilator-associated pneumonia by oral decontamination. A prospective, randomized, double-blind, placebo- controlled study. Am J Respir Crit Care Med 2001; 164: 382-388. 25. Gaussorgues Ph, Salord F, Sirodot M, Tigaud S, Cagnin S, Gerard M et al. Nosocomial bacteremia in patients under mechanical ventilation and receiving beta-inotropic drugs: efficacy of digestive decontamination. Rean Soins Intens Med Urg 1991; 7: 169-174. 26. Korinek AM, Laisne MJ, Nicolas MH, Raskine L, Deroin V, Sanson-Lepors MJ. Selective decontamination of the digestive tract in neuro-surgical intensive care unit patients: A double-blind, randomized, placebo- controlled study. Crit Care Med 1993; 21: 1466-1473. 27. Krueger WA, Lenhart FP, Neeser G, Ruckdeschel G, Schreckhase H, Eissner HJ et al. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients. A prospective, stratified, randomized, double-blind, placebo-controlled clinical trial. Am J Respir Crit Care Med 2002; 166: 1029-1037. 28. Pugin J, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomized, placebo-controlled, double-blind clinical trials. JAMA 1991; 265: 2704-2710. 29. Schardey HM, Joosten U, Finke U, Staubach KH, Schauer R, Heiss A et al. The prevention of anastomotic leakage after total gastrectomy with local decontamination. A prospective, randomized, double-blind, placebo- controlled multicenter trial. Ann Surg 1997; 225: 172-180. 30. Hammond JMJ, Potgieter PD. Long-term effects of selective decontamination on antimicrobial resistance. Crit Care Med 1995; 23: 637- 645. 31. Stoutenbeek CP, van Saene HKF, Zandstra DF. The effect of oral non- absorbable antibiotics on the emergence of resistant bacteria in patients in an intensive care unit. J Antimicrob Chemother 1987; 19: 513-520. 32. Lingnau W, Berger J, Javorsky F, Fille M, Allenberger F, Benzer H. Changing bacterial ecology during a five year period of selective intestinal decontamination. J Hosp Infect 1998; 39: 195-206. 33. Sarginson RE, Taylor N, Reilly N, Baines PB, van Saene HKF. Infection in prolonged pediatric critical illness. A prospective four-year study based on knowledge of the carrier state. Crit Care Med 2004; 32: 839-847. 34. Leone M, Albanese J, Antonini F, Nguyen-Michel A, Martin C. Long-term [6 year] effect of selective digestive decontamination on antimicrobial resistance in intensive care, multitrauma patients. Crit Care Med 2003; 31: 2090-2095. 35. de la Cal MA, Cerda E, van Saene HKF, Garcia-Hierro P, Negro E, Parra ML et al. Effectiveness and safety of enteral vancomycin to control endemicity of methicillin-resistant Staphylococcus aureus in a medical/surgical intensive care unit. J Hosp Infect 2004; 56: 175-183. 36. Tetteroo GWM, Wagenvoort JHT, Bruining HA. Bacteriology of selective decontamination: efficacy and rebound colonization. J Antimicrob Chemother 1994; 34: 139-148. 37. Abella A, de la Cal MA, Cerda E, Lopez L, Alia I, Garcia-Hierro P et al. Control of MRSA endemicity with enteral vancomycin in a burn intensive care unit. Intensive Care Med 2004; 30 [Suppl 1]: Abstract 556, p S145. 38. Andersen HC. Hans Christian Andersen's Fairy Tales [The Classic Children's Treasury] Running Press, 1996.
Dodek P, Keenan S, Cook D, Heyland D, Jacka M, Hand L, et al. Evidence-Based Clinical Practice Guideline for the Prevention of Ventilator-Associated Pneumonia. Ann Intern Med. 2004;141:305–313. doi: 10.7326/0003-4819-141-4-200408170-00011
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Published: Ann Intern Med. 2004;141(4):305-313.
Guidelines, Infectious Disease, Mechanical Ventilation, Pneumonia, Pulmonary/Critical Care.
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